7-methyl-3-methylene-7-octenal acetal compund and methods for producing aldehyde compound and ester compound using the same

ABSTRACT

There are provided methods of efficiently producing compounds that are, for example, sex pheromones of San Jose Scale. For example, there is provided a method for producing a 7-methyl-3-methylene-7-octenyl carboxylate compound (4), the method including the steps of: hydrolyzing a 7-methyl-3-methylene-7-octenal acetal compound (1) to obtain 7-methyl-3-methylene-7-octenal (2); reducing the 7-methyl-3-methylene-7-octenal (2) to obtain 7-methyl-3-methylene-7-octenol (3); and esterifying the 7-methyl-3-methylene-7-octenol (3) to obtain a 7-methyl-3-methylene-7-octenyl carboxylate compound (4).

RELATED APPLICATION

The following application is a divisional application of U.S.Non-Provisional application Ser. No. 15/825,299 filed Nov. 29, 2017,which is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The invention relates to a 7-methyl-3-methylene-7-octenal acetalcompound and methods for producing an aldehyde compound and an estercompound using the acetal compound.

2. Related Art

3,7-Dimethyl-2,7-octadienal and a corresponding alcohol,3,7-dimethyl-2,7-octadienol are widely applied as floral perfumes andfruit flavors. Their regioisomers having double bonds at differentpositions, 7-methyl-3-methylene-7-octenal and7-methyl-3-methylene-7-octenol, are expected to be applied in the samefields. Stoyanova et al. have reported that7-methyl-3-methylene-7-octenal exists in the essential oil of seeds ofAmomum tsaoko (Godoshnik na Visshiya Khimikotekhnologicheski Institut,Sofiya, 31, 203 (1991), CODEN: GVKIAH, ISSN: 0489-6211).

Quadraspidiotus perniciosus (generic name: San Jose Scale, hereinafterabbreviated as “SJS”) is widely distributed in the world, damages fruittrees and ornamental trees, especially deciduous fruit trees, and thusis an economically critical insect pest. Gieselmann et al. and Andersonet al. have found that the sex pheromone of SJS contains three activecomponents of 7-methyl-3-methylene-7-octenyl propionate,(Z)-3,7-dimethyl-2,7-octadienyl propionate, and(E)-3,7-dimethyl-2,7-octadienyl propionate (Gieselmann et al., J. Chem.Ecol., 5, 891 (1979), Anderson et al., J. Chem. Ecol., 5, 919 (1979),and Anderson et al., J. Chem. Ecol., 7, 695 (1981)).

An insect sex pheromone is a biologically active substance that iscommonly secreted by female individuals to attract male individuals, anda small amount of the sex pheromone shows strong attractive activities.A sex pheromone has been widely used as means for forecasting insectemergence or for ascertaining regional spread (invasion into a specificarea) and as means for controlling an insect pest. As the means forcontrolling the insect pest, control methods called mass trapping, lureand kill (another name: attract and kill), lure and infect (anothername: attract and infect), and mating disruption are widely used inpractice. To utilize a sex pheromone, it is necessary to economicallyproduce a required amount of the sex pheromone product for basicresearch and also for application.

Synthetic examples of the SJS sex pheromones include the followingSyntheses (a) to (f):

Synthesis (a): syntheses of 7-methyl-3-methylene-7-octenyl propionateand (Z)-3,7-dimethyl-2,7-octadienyl propionate by Anderson et al.,containing addition of an organocuprate reagent to an alkyne as the keyreaction (Anderson et al., J. Chem. Ecol., 5, 919 (1979));

Synthesis (b): syntheses of 7-methyl-3-methylene-7-octenyl propionate,(Z)-3,7-dimethyl-2,7-octadienyl propionate and(E)-3,7-dimethyl-2,7-octadienyl propionate by Weiler et al., containinga one-carbon homologation step from a β-keto ester compound:7-methyl-3-oxo-7-octenoate (Weiler et al., Can. J. of Chemistry, 71,1955 (1993));

Synthesis (c): synthesis of 7-methyl-3-methylene-7-octenyl propionate byWeedon et al., containing photochemical regioisomerization of a doublebond from an α,β-unsaturated ester to a β,γ-unsaturated ester as the keyreaction (A. C. Weedon et al., Tetrahedron Letters, 27, 5555 (1986));

Synthesis (d): synthesis of 7-methyl-3-methylene-7-octenyl propionate byZhang et al. containing formation of exo-methylene as the key reactionthrough reduction of an allylic chloride obtained by chlorinationinvolving isomerization of a trisubstituted double bond (H. S. Zhang etal., Chinese Chemical Letters, 2, 611 (1991), and Zhang et al., HuaxueTongbao, 40, (1994));

Synthesis (e): synthesis of 7-methyl-3-methylene-7-octenyl propionatethrough alkylation of a dianion of 3-methyl-3-buten-1-ol by Anderson etal. and Chong et al. (Anderson et al., J. Chem. Ecol., 7, 695 (1981),and J. M. Chong et al., J. of Org. Chem., 66, 8248 (2001)); and

Synthesis (f): non-selective synthesis of 7-methyl-3-methylene-7-octenylpropionate through an allylic chloride mixture by Veselovskii et al. (V.V. Veselovskii et al., Izvestiya Akademii Nauk SSSR, SeriyaKhimicheskaya, 3, 591 (1990)).

SUMMARY OF THE INVENTION

In the report by R. Stoyanova et al., 0.58% of the essential oil ofseeds of Amomum tsaoko is identified as 7-methyl-3-methylene-7-octenalby a mass spectrum. However, there is no description other than the massspectrum. Synthesis of 7-methyl-3-methylene-7-octenal is not reported.

The conventional synthetic methods bring various difficulties toindustrially produce SJS sex pheromone compounds at high yields. Forexample, the difficulties arise from the use of reagents that areexpensive or difficult to handle on an industrial scale, includingorganolithium reagents such as n-butyllithium and methyllithium[Syntheses (b) and (e)], lithium aluminum hydride (LAH) [Syntheses (a),(b) and (d)], a stoichiometric amount of an organocuprate reagent[Synthesis (a)], a Tebbe reagent [Synthesis (b)], and sulfuryl chloride[Synthesis (f)]. In the photochemical isomerization with intentionaldouble bond isomerization [Synthesis (c)], difficulties arise fromformation of an undesired isomer as a by-product and its removal. Inisomerization of another double bond [Syntheses (d) and (f)],significant difficulties arise because a target compound is difficult toseparate from isomers thereof, thereby lowering the yield. In Syntheses(a) to (f), intermediates and a target compound are isolated or purifiedby various types of chromatography, which are difficult to perform on anindustrial scale.

As described above, the conventional syntheses are considered to be verydifficult to economically and industrially produce a sufficient amountof a sex pheromone product. Hence, an efficient production methodcapable of supplying a sufficient amount of a sex pheromone compound isindustrially important.

The three components contained by the SJS sex pheromone composition havesubstantially the same attractive activity, and any one of the threecomponents may be used in practical use. However, the future developmentof resistance for a long-term use can be considered to be suppressed byuse of a mixture of the components derived from the insect rather thanby single use of any one of the three components.

Hence, a method of producing all of the three components as the SJS sexpheromones from a common intermediate will eliminate the necessity ofseparately producing each of the three components. Such a method is ofindustrial significance.

As a result of intensive studies on a 7-methyl-3-methylene-7-octenalacetal compound (1) as an candidate of the common intermediate forsolving the problem, the inventors have found that the compound (1) canbe produced by an industrially easy and practical method. The inventorshave also found that, from the intermediate,7-methyl-3-methylene-7-octenal (2), a 7-methyl-3-methylene-7-octenylcarboxylate compound (4), 3,7-dimethyl-2,7-octadienal (5), a3,7-dimethyl-2,7-octadienyl carboxylate compound (7), and a mixture of a7-methyl-3-methylene-7-octenyl carboxylate compound (4) and a3,7-dimethyl-2,7-octadienyl carboxylate compound (7) can be produced.The inventors have further found that a3-acyloxymethyl-3-methylene-butenal acetal compound (10), which can beused to produce a 7-methyl-3-methylene-7-octenal acetal compound (1),has excellent storage stability. The inventors have completed theinvention in this way.

In an aspect of the invention, there is provided a method for producing7-methyl-3-methylene-7-octenal, comprising a step of hydrolyzing a7-methyl-3-methylene-7-octenal acetal compound of General Formula (1) toobtain 7-methyl-3-methylene-7-octenal of Formula (2).

In another aspect of the invention, there is provided a method forproducing a 7-methyl-3-methylene-7-octenyl carboxylate compound,comprising steps of: hydrolyzing a 7-methyl-3-methylene-7-octenal acetalcompound of General Formula (1) to obtain 7-methyl-3-methylene-7-octenalof Formula (2); reducing the 7-methyl-3-methylene-7-octenal (2) toobtain 7-methyl-3-methylene-7-octenol of Formula (3); and esterifyingthe 7-methyl-3-methylene-7-octenol (3) to obtain a7-methyl-3-methylene-7-octenyl carboxylate compound of General Formula(4).

In still another aspect of the invention, there is provided a method forproducing 3,7-dimethyl-2,7-octadienal, comprising steps of: hydrolyzinga 7-methyl-3-methylene-7-octenal acetal compound of General Formula (1)to obtain 7-methyl-3-methylene-7-octenal of Formula (2); and isomerizingthe 7-methyl-3-methylene-7-octenal (2) in the presence of a base toobtain 3,7-dimethyl-2,7-octadienal of Formula (5).

In a further aspect of the invention, there is provided a method forproducing a 3,7-dimethyl-2,7-octadienyl carboxylate compound, comprisingsteps of: hydrolyzing a 7-methyl-3-methylene-7-octenal acetal compoundof General Formula (1) to obtain 7-methyl-3-methylene-7-octenal ofFormula (2); isomerizing the 7-methyl-3-methylene-7-octenal (2) in thepresence of a base to obtain 3,7-dimethyl-2,7-octadienal of Formula (5);reducing the 3,7-dimethyl-2,7-octadienal (5) to obtain3,7-dimethyl-2,7-octadienol of Formula (6); and esterifying the3,7-dimethyl-2,7-octadienol (6) to obtain a 3,7-dimethyl-2,7-octadienylcarboxylate compound of General Formula (7).

In a still further aspect of the invention, there is provided a7-methyl-3-methylene-7-octenal acetal compound of General Formula (1).

In an aspect of the invention, there is provided a method for producinga 7-methyl-3-methylene-7-octenal acetal compound, comprising a step ofcoupling a nucleophilic reagent expressed as a 3-methyl-3-butenyl M ofGeneral Formula (8) with an acetal compound of General Formula (9) toobtain a 7-methyl-3-methylene-7-octenal acetal compound of GeneralFormula (1).

In an aspect of the invention, there is provided a3-acyloxymethyl-3-butenal acetal compound of General Formula (10).

In another aspect of the invention, there is provided a method forsimultaneously producing a 7-methyl-3-methylene-7-octenyl carboxylatecompound and a 3,7-dimethyl-2,7-octadienyl carboxylate compound,comprising steps of: subjecting a 7-methyl-3-methylene-7-octenal acetalcompound of General Formula (1) to hydrolysis and isomerization toobtain a first mixture of 7-methyl-3-methylene-7-octenal of Formula (2)and 3,7-dimethyl-2,7-octadienal of Formula (5), wherein an acid or abase is present in the isomerization; reducing the first mixture toobtain a second mixture of 7-methyl-3-methylene-7-octenol of Formula (3)and 3,7-dimethyl-2,7-octadienol of Formula (6); and esterifying thesecond mixture to obtain a third mixture of a7-methyl-3-methylene-7-octenyl carboxylate compound of Formula (4) and a3,7-dimethyl-2,7-octadienyl carboxylate compound of General Formula (7).

In the formulae, R¹ and R², which may be the same or different, are eachan alkyl group having 1 to 6 carbon atoms, or are bonded to each otherto form a divalent alkylene group having 2 to 12 carbon atoms; R³ is amonovalent hydrocarbon group having 1 to 6 carbon atoms; M is a cationicmoiety; X is a leaving group; and X¹ is an acyloxy group having 1 to 6carbon atoms.

According to the invention, a 7-methyl-3-methylene-7-octenal acetalcompound (1), which is a useful intermediate, can be used as a commonintermediate to efficiently produce 7-methyl-3-methylene-7-octenal (2),a 7-methyl-3-methylene-7-octenyl carboxylate compound (4),3,7-dimethyl-2,7-octadienal (5), a 3,7-dimethyl-2,7-octadienylcarboxylate compound (7), a mixture of a 7-methyl-3-methylene-7-octenylcarboxylate compound (4) and a 3,7-dimethyl-2,7-octadienyl carboxylatecompound (7), or a 7-methyl-3-methylene-7-octenal acetal compound (1).In addition, a 3-acyloxymethyl-3-methylene-butenal acetal compoundhaving excellent storage stability can be used to efficiency produce a7-methyl-3-methylene-7-octenal acetal compound (1). In particular,7-methyl-3-methylene-7-octenyl propionate,(Z)-3,7-dimethyl-2,7-octadienyl propionate, and(E)-3,7-dimethyl-2,7-octadienyl propionate, which are SJS sexpheromones, can be simultaneously produced.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The chemical formulae of intermediates, reagents, and target compoundsin the specification can include stereoisomers such as enantiomers anddiastereomers in terms of structure. Each chemical formula is intendedto represent all the isomers in each case unless otherwise stated. Theisomer may be used alone or as a mixture of two or more isomers.

The inventors have studied the following synthetic strategy. As anexample of the 7-methyl-3-methylene-7-octenyl carboxylate compound, apropionate will be described. It is considered that the target compound7-methyl-3-methylene-7-octenyl propionate (A) can also be produced if7-methyl-3-methylene-7-octenal (C), which is one of the target compoundsin the invention, can be synthesized, because reduction of the aldehyde(C) into 7-methyl-3-methylene-7-octenol (B) and subsequentesterification of the alcohol (B) result in ester (A). It is consideredthat the 7-methyl-3-methylene-7-octenal (C) can be produced if acorresponding 7-methyl-3-methylene-7-octenal acetal compound (D) can behydrolyzed in a mild condition without double-bond migration. It isconsidered that the 7-methyl-3-methylene-7-octenal acetal compound (D)can be synthesized by the coupling reaction of two building blocks eachhaving 5 carbon atoms, in the other words, the coupling reaction betweenan organometallic reagent (E) as a nucleophilic reagent and anelectrophilic reagent having a leaving group X at the allylic positionand having 5 carbon atoms (F). On the other hand, it is considered that3,7-dimethyl-2,7-octadienyl propionate (G), which is one of the targetcompounds in the invention, can be produced if a corresponding3,7-dimethyl-2,7-octadienal (I) can be synthesized, because reduction ofthe aldehyde (I) into 3,7-dimethyl-2,7-octadienol (H) and subsequentesterification of the alcohol (H) results in the ester (G). It isconsidered that the 3,7-dimethyl-2,7-octadienal (I) can be produced ifthe exo-double bond at 3-position of 7-methyl-3-methylene-7-octenal (C)can be isomerized into a tri-substituted, conjugated double bond, whichis considered to be thermodynamically more stable.

In the scheme, hollow arrows represent transformation in theretrosynthetic analysis, X is a leaving group, and M is a cationicmoiety. Chemical Formula (G) means (Z)-3,7-dimethyl-2,7-octadienylpropionate of Formula (Gz), (E)-3,7-dimethyl-2,7-octadienyl propionateof Formula (Ge), or a mixture thereof. Chemical Formula (H) represents(Z)-3,7-dimethyl-2,7-octadienol of Formula (Hz),(E)-3,7-dimethyl-2,7-octadienol of Formula (He), or a mixture thereof.Chemical Formula (I) represents (Z)-3,7-dimethyl-2,7-octadienal ofFormula (Iz), (E)-3,7-dimethyl-2,7-octadienal of Formula (Ie), or amixture thereof.

In other words, 7-methyl-3-methylene-7-octenal (C) produced byhydrolysis of a 7-methyl-3-methylene-7-octenal acetal compound (D) canbe converted into both 7-methyl-3-methylene-7-octenol (B) and3,7-dimethyl-2,7-octadienol (H), so that a7-methyl-3-methylene-7-octenyl carboxylate compound and a3,7-dimethyl-2,7-octadienyl carboxylate compound can be simultaneouslysynthesized.

Embodiments of the invention will now be described in detail.

[1] Method for Producing 7-methyl-3-methylene-7-octenal acetal Compound(1)

A 7-methyl-3-methylene-7-octenal acetal compound (1) may be produced bya coupling reaction between a nucleophilic reagent expressed as a3-methyl-3-butenyl M (8) and an acetal compound (9) having a leavinggroup X. In the formulae below, M is a cationic moiety, X is a leavinggroup, and R¹ and R², which may be the same or different, are each analkyl group having 1 to 6 carbon atoms, or are bonded to each other toform a divalent alkylene group having 2 to 12 carbon atoms.

The nucleophilic reagent 3-methyl-3-butenyl M (8) to be used in thecoupling reaction is exemplified by a nucleophilic reagent3-methyl-3-butenyl M containing a group I or group II metal element ofthe periodic table or a transition metal element.

Among the nucleophilic reagent 3-methyl-3-butenyl M containing a group Ior group II metal element, a 3-methyl-3-butenyl lithium reagent(organolithium reagent) and a 3-methyl-3-butenyl magnesium halide(Grignard reagent) are preferred from the standpoint of reactivity,selectivity, easy preparation and the like.

The nucleophilic reagent 3-methyl-3-butenyl M containing a transitionmetal element to be used in the coupling reaction may be prepared by ametal exchange reaction of the organolithium reagent or the Grignardreagent with a stoichiometric amount (1 mol) or more of a transitionmetal compound, or may be formed in the coupling reaction system fromthe organolithium reagent or the Grignard reagent with a transitionmetal compound catalyst.

Examples of the transition metal compound to be used in the couplingreaction include transition metal compounds containing copper, iron,nickel, palladium, zinc, silver, or another transition metal.Particularly preferred are copper compounds such as copper(I) chloride,copper(I) bromide, copper(I) iodide, copper(I) cyanide, copper(I) oxide,copper(II) chloride, copper(II) bromide, copper(II) iodide, copper(II)cyanide, copper(II) oxide, and dilithium tetrachlorocuprate (Li₂CuCl₄).

The amount of the transition metal compound to be used in the couplingreaction is a catalytic amount (0.0001 to 0.999 mol) to a stoichiometricamount (1 mol) or an excess amount (more than 1 mol and 100 mol or less)relative to 1 mol of the acetal compound (9) having a leaving group X.It is particularly preferably the catalytic amount from the standpointof economy and safety.

When a transition metal compound is used in the coupling reaction, aphosphorus compound such as a trialkyl phosphite (e.g. triethylphosphite) and triarylphosphine (e.g. triphenylphosphine) may also beused from the standpoint of enhancement in solubility of the transitionmetal compound in a solvent.

The cationic moiety M in the nucleophilic reagent 3-methyl-3-butenyl M(8) to be used in the coupling reaction is particularly preferably Li,MgZ, ZnZ, Cu, CuZ, or CuLiZ, wherein Z is a halogen atom or a3-methyl-3-butenyl group, from the standpoint of easy preparation of thereagent and reactivity. The nucleophilic reagent 3-methyl-3-butenyl M(8) is typically prepared by a conventional method from a3-methyl-3-butenyl halide, which is a corresponding halide. The halideis preferably a chloride, a bromide, or an iodide.

An acetal compound (9) having a leaving group X, which is the otherreactant to be used in the coupling reaction, will be described.Examples of the leaving group X in the acetal compound (9) having theleaving group X include a halogen atom, an acyloxy group, an alkoxygroup, an aryloxy group, an alkanesulfonyloxy group, and anarenesulfonyloxy group, which function as a leaving group (anionicmoiety) in the coupling reaction. Specifically preferred is a halogenatom or an acyloxy group. The halogen atom is preferably a chlorine atomor a bromine atom, and is particularly preferably a chlorine atom fromthe standpoint of reactivity and storage stability of the acetalcompound (9) having a leaving group X. The acyloxy group is preferablyan acyloxy group having 1 to 6 carbon atoms, and is specificallyexemplified by unsubstituted or halogen-substituted acyloxy groups suchas a formyloxy group, an acetoxy group, a chloroacetyloxy group, apropionyloxy group, a butyryloxy group, a hexanoyloxy group, adichloroacetyloxy group, a trichloroacetyloxy group and atrifluoroacetyloxy group. The acetoxy group is particularly preferredfrom the standpoint of reactivity, industrial availability of a rawmaterial, price, and storage stability of the acetal compound (9) havinga leaving group X. Examples of the alkoxy group include a methoxy groupand an ethoxy group. Examples of the aryloxy group include a phenoxygroup. Examples of the alkanesulfonyloxy group include amethanesulfonyloxy group, a trifluoromethanesulfonyloxy group, and abutanesulfonyloxy group. Examples of the arenesulfonyloxy group includea benzenesulfonyloxy group, a p-toluenesulfonyloxy group, and anaphthalenesulfonyloxy group.

In the acetal compound (9) having a leaving group X, R¹ and R², whichmay be the same or different, are each an alkyl group having 1 to 6carbon atoms, or are bonded to each other to form a divalent alkylenegroup having 2 to 12 carbon atoms. Examples of the alkyl group having 1to 6 carbon atoms include a linear primary alkyl group such as a methylgroup, an ethyl group, an n-propyl group, an n-butyl group, an n-pentylgroup and an n-hexyl group; a branched primary alkyl group such as anisobutyl group, a 3-methylbutyl group, a neopentyl group and a4-methylpentyl group; a secondary alkyl group such as an isopropylgroup, a sec-butyl group, a 1-methylbutyl group, a 1,2-dimethylpropylgroup and a 1-methylpentyl group; and a tertiary alkyl group such as at-butyl group and a 1,1-dimethylpropyl group. Examples of the divalentalkylene group having 2 to 12 carbon atoms include an ethylene group, a1,2-propylene group, a 1,3-propylene group, a 1,2-butylene group, a1,3-butylene group, a 2,3-butylene group, a 1,4-butylene group, and a2,2-dimethyl-1,3-propylene group. For R¹ and R², the alkyl group having1 to 6 carbon atoms is preferably a linear primary alkyl group,particularly preferably a methyl group or an ethyl group from thestandpoint of easy synthesis or availability of a raw material, price,the reactivity in the hydrolysis described later and the like. Thedivalent alkylene group having 2 to 10 carbon atoms is preferably anethylene group, a 1,2-propylene group, a 1,3-propylene group, or a1,2-butylene group.

The acetal compound (9) having a leaving group X as a reactant in thecoupling reaction has the leaving group X at the allylic position, sothat the attack site by the nucleophilic reagent 3-methyl-3-butenyl M(8) on the acetal compound (9) having the leaving group X can be eitherthe carbon atom bonded to X or the methylene carbon of the exo-doublebond. The S_(N)2 substitution reaction proceeds in the former case,while the S_(N)2′ substitution reaction involving allylic rearrangementproceeds in the latter case. In either case, a7-methyl-3-methylene-7-octenal acetal compound (1) is produced.

The amounts of the nucleophilic reagent 3-methyl-3-butenyl M (8) and theacetal compound (9) having a leaving group X to be used in the couplingreaction may be selected in consideration of the substrate type,reaction conditions, reaction yield, and economy such as the price of anintermediate. The amount of the nucleophilic reagent 3-methyl-3-butenylM (8) is preferably 0.02 to 100 mol, more preferably 0.2 to 10 mol, evenmore preferably 0.5 to 5 mol relative to 1 mol of the acetal compound(9) having a leaving group X.

Examples of the solvent to be used in the coupling reaction preferablyinclude an ether such as diethyl ether, di-n-butyl ether, t-butyl methylether, cyclopentyl methyl ether, tetrahydrofuran and 1,4-dioxane. Suchan ether may be used together with a hydrocarbon such as hexane,heptane, benzene, toluene, xylene and cumene, or may be used togetherwith an aprotic polar solvent such as N,N-dimethylformamide (DMF),N,N-dimethylacetamide, N,N-dimethylpropionamide,1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO) andhexamethylphosphoric triamide (HMPA).

In the coupling reaction step, a lithium salt such as lithium chloride,lithium bromide and lithium iodide may be used as a reaction catalyst inan amount of 0.0001 to 5 mol relative to 1 mol of the acetal compound(9).

The reaction temperature of the coupling reaction is preferably −78° C.to the boiling point of a solvent, more preferably −10° C. to 100° C.

The reaction time of the coupling reaction may be freely selected and ispreferably optimized by monitoring the progress of the reaction by meansof gas chromatography (GC) or thin-layer chromatography (TLC).Typically, the reaction time is preferably 5 minutes to 240 hours.

When a 7-methyl-3-methylene-7-octenal acetal compound (1) obtained bythe above coupling reaction has a sufficient purity, the crude productmay be subjected to the next step directly, or may be purified by amethod appropriately selected from purification methods commonly used inorganic syntheses, such as distillation and various types ofchromatography. The distillation is particularly preferred from thestandpoint of industrial economy.

Examples of a method for producing a 3-halomethyl-3-butenal acetalcompound (9) having a halogen as the leaving group X include a methodfor producing 3-bromomethyl-3-butenal diethyl acetal (X═Br, R¹═R²═C₂H₅)described in the article by I. V. Mineeva et al., Russian Journal ofOrganic Chemistry, 45, 1623, (2009). The 3-bromomethyl-3-butenal diethylacetal may be used as a reactant in the coupling reaction in accordancewith the invention. The diethyl acetal is a yellowish liquid immediatelyafter the preparation, but is rapidly discolored to yellow, brown, andthen black even when stored with cooling under nitrogen, and the puritymarkedly deteriorates for a long-time storage. In addition, the diethylacetal is difficult to purify by an industrial method.

In contrast, a 3-acyloxymethyl-3-butenal acetal compound, which may beprepared by a substitution reaction of replacing the bromine atom of a3-bromomethyl-3-butenal acetal compound by an acyloxy group, ispreferable because it exhibits sufficient reactivity as a reactant inthe coupling reaction in accordance with the invention, is relativelystable during a long-term storage, and can be purified by an industrialmethod such as vacuum distillation. Examples of the3-acyloxymethyl-3-butenal acetal compound preferably include a compoundof General Formula (10). In the formula, X¹ is an acyloxy group having 1to 6 carbon atoms.

Examples of the substitution reaction of replacing the bromine atom byan acyloxy group include thermally reacting a 3-bromomethyl-3-butenalacetal compound with a carboxylate salt corresponding to a target acylgroup in a solvent.

Examples of the carboxylate salt include an alkali metal salt such as asodium salt, a lithium salt and a potassium salt, and an alkaline earthmetal salt such as a magnesium salt and a barium salt.

The amount of the carboxylate salt is preferably 1 to 500 mol, morepreferably 1 to 50 mol, even more preferably 1 to 5 mol relative to 1mol of the 3-bromomethyl-3-butenal acetal compound.

Examples of the solvent for the reaction preferably include water;hydrocarbons such as hexane, heptane, benzene, toluene, xylene andcumene; ethers such as diethyl ether, dibutyl ether, diethylene glycoldiethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran and1,4-dioxane; alcohols such as methanol, ethanol, 1-propanol, 2-propanol,ethylene glycol monomethyl ether and diethylene glycol monomethyl ether;nitriles such as acetonitrile; ketones such as acetone and 2-butanone;esters such as ethyl acetate and n-butyl acetate; and aprotic polarsolvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide and hexamethylphosphoric triamide. The solvent may be usedsingly or in combination of two or more thereof. The aprotic polarsolvent or a mixed solvent containing the aprotic polar solvent isparticularly preferred from the standpoint of reaction rate and thelike.

An appropriate reaction temperature may be selected depending on acarboxylate salt to be used or reaction conditions. It is typicallypreferably room temperature (i.e. 5 to 35° C., hereinafter the samedefinition for the room temperature) to the boiling point temperature ofa solvent.

An acetal compound having a different leaving group including a3-alkoxymethyl-3-butenal acetal compound, a 3-aryloxymethyl-3-butenalacetal compound, a 3-alkanesulfonyloxymethyl-3-butenal acetal compound,and a 3-arenesulfonyloxymethyl-3-butenal acetal compound may also beproduced by a conventional method.

[2] Method for Producing 7-methyl-3-methylene-7-octenal acetal Compound(1) by Transacetalization

A 7-methyl-3-methylene-7-octenal acetal compound (1) having certainsubstituents as R¹ and R² may be converted through transacetalizationinto another compound (1) having other substituents as R¹ and R² inconsideration of ease in purification due to a change in physicalproperties such as boiling point, storage stability, the reactivity inthe subsequent hydrolysis and the like. The transacetalization will bedescribed in Examples below, and may be carried out, for example, byheating the reactant acetal with an alcohol constituting an intendedacetal in an acid catalyst condition. In the acid catalytictransacetalization, it is found that the conversion from a compound (1)having certain substituents as R¹ and R² to another compound (1) havingother substituents as R¹ and R² proceeds at a high yield without sidereactions such as regioisomerization of a double bond. For thesereasons, the transacetalization is favorable as compared with thesynthetic method in which a compound (1) having certain substituents asR¹ and R² is hydrolyzed into 7-methyl-3-methylene-7-octenal (2), andthen the octenal (2) is subjected to acetalization into another compound(1) having other substituents as R¹ and R².

[3] Method for Producing 7-methyl-3-methylene-7-octenal (2)

Production of 7-methyl-3-methylene-7-octenal (2) by hydrolysis of a7-methyl-3-methylene-7-octenal acetal compound (1) will next bedescribed.

The hydrolysis may be selected from various reactions known as theconversion reaction of an acetal into an aldehyde. The hydrolysis ispreferably carried out in the presence of water under an acidiccondition from the standpoint of industrial economy. For the reaction,an auxiliary solvent may be used together with the water.

Examples of the acid to be used for the hydrolysis include inorganicacids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitricacid, phosphoric acid and silica gel; organic acids such as formic acid,acetic acid, propionic acid, oxalic acid, chloroacetic acid,dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid,methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid;and acidic ion exchange resins such as Amberlyst-15. The acid is usedsingly or in combination of two or more thereof. Specifically,hydrochloric acid as an inorganic acid, and formic acid, acetic acid,propionic acid and oxalic acid as organic acids are particularlypreferable because they are inexpensive and industrially available inlarge amounts.

The amount of the acid to be used in the hydrolysis depends on R¹, R²and a type of the acid. It is preferably 0.0001 to 1000 mol, morepreferably 0.001 to 100 mol relative to 1 mol of the7-methyl-3-methylene-7-octenal acetal compound (1).

Examples of the auxiliary solvent to be used in the hydrolysis includechlorinated solvents such as methylene chloride, chloroform andtrichloroethylene; hydrocarbons such as hexane, heptane, benzene,toluene, xylene and cumene; ethers such as diethyl ether, dibutyl ether,diethylene glycol diethyl ether, diethylene glycol dimethyl ether,tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether anddiethylene glycol dimethyl ether; alcohols such as methanol, ethanol,1-propanol, 2-propanol, tert-butyl alcohol, ethylene glycol monomethylether and diethylene glycol monomethyl ether; nitriles such asacetonitrile and propionitrile; ketones such as acetone and 2-butanone;esters such as ethyl acetate and n-butyl acetate; and aprotic polarsolvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide and hexamethylphosphoric triamide. The solvent may be usedsingly or in combination of two or more thereof.

The reaction temperature of the hydrolysis may be appropriately selecteddepending on a type of the acid or solvent to be used and reactionconditions. Typically, it is preferably −20° C. to a boiling point ofthe solvent, more preferably −20° C. to room temperature.

The reaction time may be freely selected and is preferably optimized bymonitoring the reaction by means of gas chromatography (GC) orthin-layer chromatography (TLC). Typically, the reaction time ispreferably 5 minutes to 240 hours.

When 7-methyl-3-methylene-7-octenal (2) is intended to be synthesizedselectively (i.e. at yield as high as possible), a mild condition,including use of an acid having low acidity, use of a large amount of asolvent to reduce the substrate concentration in a reaction mixture, alower reaction temperature and suppression of reaction rate to a degreefor easy control, is selected from the above hydrolysis conditions toprevent isomerization of a double bond.

On the contrary, along with the synthesis of7-methyl-3-methylene-7-octenal (2), the compound (2) may be allowed toundergo conversion involving the regioisomerization of a double bondinto 3,7-dimethyl-2,7-octadienal (5). As a result, a mixture ofcompounds (2) and (5) may be intentionally and simultaneouslysynthesized.

In the simultaneous productions, the production ratio of the compound(2) to the compound (5), and the production ratio of (5z) and (5e),which are geometric isomers of the compound (5), may be considered. Thispoint will be described later.

It is also preferable to monitor the progresses of the hydrolysis andthe isomerization by means of gas chromatography (GC) or thin-layerchromatography (TLC) to stop the reaction at an intended ratio. However,when 3,7-dimethyl-2,7-octadienal (5) is intended to be selectivelyproduced, a method of isomerizing 7-methyl-3-methylene-7-octenal (2)into 3,7-dimethyl-2,7-octadienal (5) in a basic condition is better thanthe hydrolysis in an acidic condition to completely obtain3,7-dimethyl-2,7-octadienal (5), as described later.

When the 7-methyl-3-methylene-7-octenal (2) produced by the abovehydrolysis has a sufficient purity, the crude product may be subjectedto the next step directly, or may be purified by a method appropriatelyselected from purification methods commonly used in organic syntheses,such as distillation and various types of chromatography. Thedistillation is particularly preferable from the standpoint ofindustrial economy.

[4] Method for Producing 7-methyl-3-methylene-7-octenol (3)

The formyl group of the 7-methyl-3-methylene-7-octenal (2) producedabove is reduced to obtain a corresponding7-methyl-3-methylene-7-octenol (3).

The reduction may be selected from known reduction reactions from analdehyde to an alcohol. In a typical reduction, a reactant in a solventis reacted with a reducing agent, while being optionally cooled orheated.

Examples of the reducing agent to be used for the reduction includehydrogen; boron compounds such as borane, alkylboranes, dialkylboranesand bis(3-methyl-2-butyl)borane; dialkylsilanes; trialkylsilanes;alkylaluminums; dialkylaluminums; metal hydrides such as sodium hydride,lithium hydride, potassium hydride and calcium hydride; and complexhydrides and alkoxy or alkyl derivatives thereof such as sodiumborohydride, lithium borohydride, potassium borohydride, calciumborohydride, sodium aluminum hydride, lithium aluminum hydride, sodiumtrimethoxyborohydride, lithium trimethoxyaluminum hydride, lithiumdiethoxyaluminum hydride, lithium tri-tert-butoxyaluminum hydride,sodium bis(2-methoxyethoxy)aluminum hydride, lithium triethylborohydrideand diisobutylaluminum hydride. The complex hydrides are preferable fromthe standpoint of reaction conditions, easy work-up, easy isolation of aproduct and the like.

The amount of the reducing agent to be used in the reduction variesdepending on a type of the reducing agent, reaction conditions and thelike. Typically, it is preferably 0.5 mol to an excess amount (i.e. morethan 1 mol and 1,000,000 mol or less), more preferably 0.9 to 200 molrelative to 1 mol of a substrate.

Examples of the solvent to be used in the reduction preferably includewater; hydrocarbons such as hexane, heptane, benzene, toluene, xyleneand cumene; ethers such as diethyl ether, dibutyl ether, diethyleneglycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuranand 1,4-dioxane; alcohols such as methanol, ethanol, 1-propanol,2-propanol, ethylene glycol monomethyl ether and diethylene glycolmonomethyl ether; nitriles such as acetonitrile; ketones such as acetoneand 2-butanone; esters such as ethyl acetate and n-butyl acetate; andaprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxideand hexamethylphosphoric triamide. The solvent may be used singly or incombination of two or more thereof.

The solvent to be used in the reduction is appropriately selecteddepending on a type of the reducing agent. Examples of the preferablecombination of the reducing agent and the solvent include thecombination of sodium borohydride as the reducing agent and a solventselected from the group consisting of water, an alcohol, an ether, amixed solvent of an ether and an alcohol, and a mixed solvent of anether and a hydrocarbon; and the combination of lithium aluminum hydrideas the reducing agent and a solvent selected from the group consistingof an ether, and a mixed solvent of an ether and a hydrocarbon.

The reaction temperature of the reduction varies depending on a type ofthe reducing reagent or the solvent to be used. For example, whenlithium aluminum hydride in tetrahydrofuran is used as the reducingagent, the reaction temperature is preferably −78 to 50° C., morepreferably −70 to 20° C.

The reaction time of the reduction may be freely selected. The reactionis preferably completed by monitoring the reaction by means of gaschromatography (GC) or silica gel thin-layer chromatography (TLC) fromthe standpoint of yield. Typically, the reaction time is preferably 5 to240 hours.

The reducing agent or the reaction condition is preferably selected soas not to reduce the double bonds of the reactants (2) and/or (5).Particularly in the reduction of 3,7-dimethyl-2,7-octadienal (5) to3,7-dimethyl-2,7-octadienol (6), it is preferable to select the reducingagent or reaction condition to enhance the production of3,7-dimethyl-2,7-octadienol (6) as a target product by 1,2-reduction,while suppressing the production of 3,7-dimethyl-7-octenol as aby-product by 1,4-reduction.

When the 7-methyl-3-methylene-7-octenol (3) produced by the reductionhas a sufficient purity or a sufficient isomer ratio, the crude productmay be subjected to the next step directly, or may be subjected topurification or isomer separation by a method appropriately selectedfrom purification methods and isomer separation methods commonly used inorganic syntheses, such as distillation and various types ofchromatography. The distillation is particularly preferable from thestandpoint of industrial economy.

[5] Method for Producing 7-methyl-3-methylene-7-octenyl carboxylateCompound (4)

The 7-methyl-3-methylene-7-octenol (3) produced above may be esterifiedto obtain a corresponding 7-methyl-3-methylene-7-octenyl carboxylatecompound (4).

R³ is a hydrogen atom or a monovalent hydrocarbon group having 1 to 6carbon atoms. Examples of the monovalent hydrocarbon group having 1 to 6carbon atoms include a linear, branched or cyclic, saturated orunsaturated alkyl group, alkenyl group or aryl groups, and preferablyinclude a methyl group, an ethyl group, an n-propyl group, an n-butylgroup, an n-pentyl group, an n-hexyl group, an isopropyl group, anisobutyl group, an isopentyl group, an isohexyl group, a sec-butylgroup, a tert-butyl group, a vinyl group, an isopentenyl group, apropenyl group, an allyl group, a 1-methyl-1-propenyl group, a2-methyl-1-propenyl group, and a phenyl group.

The esterification may be selected from known ester production methodsincluding a reaction with an acylating agent, a reaction with acarboxylic acid, a transesterification, and a method in which7-methyl-3-methylene-7-octenol (3) is converted into an alkylating agentand then the alkylating agent is reacted with a carboxylic acid.

In the reaction with an acylating agent, 7-methyl-3-methylene-7-octenol(3) as a reactant is reacted, in a single solvent or a mixture of two ormore solvents, with an acylating agent and a base sequentially orsimultaneously.

Examples of the acylating agent in the reaction with the acylating agentpreferably include an acyl chloride, an acyl bromide, a carboxylicanhydride, a carboxylic trifluoroacetic anhydride, a carboxylicmethanesulfonic anhydride, a carboxylic trifluoromethanesulfonicanhydride, a carboxylic benzenesulfonic anhydride, a carboxylicp-toluenesulfonic anhydride, and p-nitrophenyl carboxylate compound.

Examples of the base to be used in the reaction with an acylating agentpreferably include triethylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine, and 4-dimethylaminopyridine.

The solvent to be used in the reaction with an acylating agent may bethe above base, or may be a single solvent or mixed solvent of two ormore solvents selected from chlorinated solvents such as methylenechloride, chloroform and trichloroethylene; hydrocarbons such as hexane,heptane, benzene, toluene, xylene and cumene; ethers such as diethylether, dibutyl ether, t-butyl methyl ether, diethylene glycol diethylether, diethylene glycol dimethyl ether, tetrahydrofuran and1,4-dioxane; nitriles such as acetonitrile; ketones such as acetone and2-butanone; esters such as ethyl acetate and n-butyl acetate; andaprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxideand hexamethylphosphoric triamide. The reaction using an acylating agentsuch as a carboxylic anhydride may be carried out with an acid catalystinstead of the base.

The amount of the acylating agent is preferably 1 to 500 mol, morepreferably 1 to 50 mol, even more preferably 1 to 5 mol relative to 1mol of 7-methyl-3-methylene-7-octenol (3).

The acid catalyst to be used instead of the base in the reaction with anacylating agent is preferably selected from inorganic acids such ashydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid;organic acids such as oxalic acid, trifluoroacetic acid, methanesulfonicacid, benzenesulfonic acid and p-toluenesulfonic acid; and Lewis acidssuch as aluminum trichloride, aluminum ethoxide, aluminum isopropoxide,aluminum oxide, boron trifluoride, boron trichloride, boron tribromide,magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride,zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide,dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide,titanium tetrachloride, titanium tetrabromide, titanium(IV) methoxide,titanium(IV) ethoxide, titanium(IV) isopropoxide, and titanium(IV)oxide.

The reaction temperature of the reaction with an acylating agent may beappropriately selected depending on a type of an acylating agent to beused and reaction conditions. Typically, it is preferably −50° C. to theboiling point of the solvent, more preferably −20° C. to roomtemperature.

The reaction with a carboxylic acid is a dehydration reaction between7-methyl-3-methylene-7-octenol (3) and the carboxylic acid, and istypically carried out with an acid catalyst.

The amount of the carboxylic acid is preferably 1 to 500 mol, morepreferably 1 to 50 mol, even more preferably 1 to 5 mol relative to 1mol of the reactant 7-methyl-3-methylene-7-octenol (3).

Examples of the acid catalyst to be used in the reaction of7-methyl-3-methylene-7-octenol (3) with a carboxylic acid includeinorganic acids such as hydrochloric acid, hydrobromic acid, sulfuricacid and nitric acid; organic acids such as oxalic acid, trifluoroaceticacid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonicacid; and Lewis acids such as aluminum trichloride, aluminum ethoxide,aluminum isopropoxide, aluminum oxide, boron trifluoride, borontrichloride, boron tribromide, magnesium chloride, magnesium bromide,magnesium iodide, zinc chloride, zinc bromide, zinc iodide, tintetrachloride, tin tetrabromide, dibutyltin dichloride, dibutyltindimethoxide, dibutyltin oxide, titanium tetrachloride, titaniumtetrabromide, titanium(IV) methoxide, titanium(IV) ethoxide,titanium(IV) isopropoxide and titanium(IV) oxide. The acid is usedsingly or in combination of two or more thereof.

The amount of the acid catalyst to be used in the reaction with acarboxylic acid is preferably 0.0001 to 100 mol, more preferably 0.001to 1 mol, even more preferably a catalytic amount of 0.01 to 0.05 molrelative to 1 mol of 7-methyl-3-methylene-7-octenol (3).

Examples of the solvent to be used in the reaction of7-methyl-3-methylene-7-octenol (3) with a carboxylic acid include thesame examples as those of the solvent to be used in the reaction with anacylating agent.

The reaction temperature of the reaction with a carboxylic acid may beappropriately selected depending on reaction conditions. Typically, itis preferably −50° C. to the boiling point of the solvent, morepreferably room temperature to the boiling point of the solvent. Asolvent containing a hydrocarbon such as hexane, heptane, benzene,toluene, xylene and cumene may be used to proceed the reaction, whilegenerated water is removed from the system by azeotropy. In this case,the water may be distilled off while the reaction mixture is refluxed atthe boiling point of the solvent at normal pressure. Alternatively, thewater may be distilled off at a temperature lower than the boiling pointunder reduced pressure.

The transesterification is carried out by reacting7-methyl-3-methylene-7-octenol (3) with an alkyl carboxylate in thepresence of a catalyst, while removing the generated alcohol. The alkylcarboxylate is preferably a primary alkyl ester of a carboxylic acid andis particularly preferably a methyl carboxylate, an ethyl carboxylate,and an n-propyl carboxylate from the standpoint of price, easy progressof the reaction and the like.

The amount of the alkyl carboxylate to be used in thetransesterification is preferably 1 to 500 mol, more preferably 1 to 50mol, even more preferably 1 to 5 mol relative to 1 mol of the reactant7-methyl-3-methylene-7-octenol (3).

Examples of the catalyst to be used in the transesterification includeinorganic acids such as hydrochloric acid, hydrobromic acid, sulfuricacid and nitric acid; organic acids such as oxalic acid, trifluoroaceticacid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonicacid; bases such as sodium methoxide, sodium ethoxide, potassiumt-butoxide and 4-dimethylaminopyridine; salts such as sodium cyanide,potassium cyanide, sodium acetate, potassium acetate, calcium acetate,tin acetate, aluminum acetate, aluminum acetoacetate and alumina; andLewis acids such as aluminum trichloride, aluminum ethoxide, aluminumisopropoxide, aluminum oxide, boron trifluoride, boron trichloride,boron tribromide, magnesium chloride, magnesium bromide, magnesiumiodide, zinc chloride, zinc bromide, zinc iodide, tin tetrachloride, tintetrabromide, dibutyltin dichloride, dibutyltin dimethoxide, dibutyltinoxide, titanium tetrachloride, titanium tetrabromide, titanium(IV)methoxide, titanium(IV) ethoxide, titanium(IV) isopropoxide andtitanium(IV) oxide. The catalyst are used singly or in combination oftwo or more thereof.

The amount of the catalyst to be used in the transesterification ispreferably 0.0001 to 100 mol, more preferably 0.001 to 1 mol, even morepreferably a catalytic amount of 0.01 to 0.05 mol relative to 1 mol of7-methyl-3-methylene-7-octenol (3).

The transesterification may be carried out without a solvent (an alkylcarboxylate as the reaction reagent may be used also as the solvent).Such a reaction is preferable from the standpoint of omission ofnecessary additional operations such as concentration and solventrecovery. A solvent may be used auxiliarily.

Examples of the solvent to be used in the transesterification preferablyinclude hydrocarbons such as hexane, heptane, benzene, toluene, xyleneand cumene; and ethers such as diethyl ether, dibutyl ether, diethyleneglycol diethyl ether, diethylene glycol dimethyl ether, tetrahydrofuranand 1,4-dioxane. The solvent is used singly or in combination of two ormore thereof.

The reaction temperature of the transesterification may be appropriatelyselected depending on a type of the alkyl carboxylate to be used andreaction conditions.

The transesterification is typically carried out with heating. Thereaction is carried out around the boiling point of a lower alcoholwhich will be generated during the transesterification. The loweralcohol is an alcohol having 1 to 3 carbon atoms and has a low boilingpoint, and examples thereof include methanol, ethanol and 1-propanol.The reaction is carried out, while the generated lower alcohol isdistilled off, to obtain good results. The alcohol may be distilled offat a temperature lower than the boiling point under reduced pressure.

In the method in which 7-methyl-3-methylene-7-octenol (3) is convertedinto an alkylating agent and then the alkylating agent is reacted with acarboxylic acid, 7-methyl-3-methylene-7-octenol (3) is converted, forexample, into a corresponding halide such as chloride, bromide andiodide, or a corresponding sulfonate such as methanesulfonate,trifluoromethanesulfonate, benzenesulfonate and p-toluenesulfonate, andis then reacted with a carboxylic acid typically in a solvent in a basiccondition. The solvent, base, reaction temperature and reaction timeare, for example, the same as those of the reaction of7-methyl-3-methylene-7-octenol (3) with an acylating agent. Instead of acombination of the carboxylic acid and the base, a carboxylate salt suchas a sodium carboxylate, a lithium carboxylate, a potassium carboxylateand an ammonium carboxylate may be used.

The 7-methyl-3-methylene-7-octenyl carboxylate compound (4) produced inthe above esterification may be subjected to purification or isomerseparation by a method appropriately selected from purification methodsor isomer separation methods commonly used in organic syntheses, such asdistillation and various types of chromatography. The distillation isparticularly preferable from the standpoint of industrial economy.

[6] Method for Producing 3,7-dimethyl-2,7-octadienal (5) and Method forSimultaneously Producing 7-methyl-3-methylene-7-octenal (2) and3,7-dimethyl-2,7-octadienal (5)

7-Methyl-3-methylene-7-octenal (2) may be subjected toregioisomerization of a double bond to obtain3,7-dimethyl-2,7-octadienal (5).

The isomerization proceeds in various conditions including an acidiccondition and a basic condition.

Examples of the acid to be used in the isomerization in the presence ofthe acid include those described in the hydrolysis of the7-methyl-3-methylene-7-octenal acetal compound (1); and Lewis acids suchas aluminum trichloride, aluminum ethoxide, aluminum isopropoxide,aluminum oxide, boron trifluoride, boron trichloride, boron tribromide,magnesium chloride, magnesium bromide, magnesium iodide, zinc chloride,zinc bromide, zinc iodide, tin tetrachloride, tin tetrabromide,dibutyltin dichloride, dibutyltin dimethoxide, dibutyltin oxide,titanium tetrachloride, titanium tetrabromide, titanium(IV) methoxide,titanium(IV) ethoxide, titanium(IV) isopropoxide and titanium(IV) oxide.An acid selected from these examples may be used in the isomerizationfrom 7-methyl-3-methylene-7-octenal (2) to 3,7-dimethyl-2,7-octadienal(5). For the isomerization, the production ratio of (5z) and (5e), whichare geometric isomers of 3,7-dimethyl-2,7-octadienal (5), may beconsidered.

The isomerization may also be allowed to proceed, while keeping thereaction conditions for hydrolysis of the 7-methyl-3-methylene-7-octenalacetal compound (1). However, severe conditions during the acidicisomerization, such as an extremely high acidic condition and a hightemperature condition, should be avoided because such sever conditionsmay lead to acid-catalyzed cyclization to generate a by-product such as2-(1,3-dimethyl-2-cyclohexenyl)ethanal.

In the isomerization in the presence of a base,7-methyl-3-methylene-7-octenal (2) is reacted with a base withoutsolvent or in a solvent. The reaction is considered to proceed throughdeprotonation and reprotonation at the α-position of the aldehyde, andthe base capable of converting the aldehyde into an enol may be used.

Examples of the base to be used in the isomerization in the presence ofthe base include ammonia; hydroxylamine; hydroxides such as lithiumhydroxide, sodium hydroxide, potassium hydroxide andtetra-n-butylammonium hydroxide; hydrides such as lithium hydride,sodium hydride and potassium hydride; alkoxides such as lithiummethoxide, lithium ethoxide, sodium methoxide, sodium ethoxide andpotassium t-butoxide; metal amides such as lithium amide, sodium amide,lithium diisopropylamide, lithium bis-trimethylsilylamide, lithiumtetramethylpiperidide and lithium isopropylcyclohexylamide; organicamines such as ethylamine, diethylamine, triethylamine,diisopropylamine, diisopropylethylamine, ethylenediamine,N,N,N′,N′-tetramethylethylenediamine, diazabicyclo[4.3.0]-5-nonene(DBN), diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]-7-undecene,aniline, N-methylaniline, N,N-dimethylaniline, N,N-diethylaniline,1-naphthylamine, 2-naphthylamine, pyridine, 4-dimethylaminopyridine,triazine, pyrrolidine, piperidine, piperazine, morpholine and imidazole;and organometallic compounds such as triphenylmethyllithium,triphenylmethylsodium, triphenylmethylpotassium, methyllithium,phenyllithium, n-butyllithium, s-butyllithium, t-butyllithium and ethylmagnesium halides. The base is used singly or in combination of two ormore thereof. The organic amines are preferable from the standpoint ofeasy reaction, a required amount, easy work-up and the like.

The amount of the base to be used in the isomerization in the presenceof the base may be a catalytic amount (0.0001 to 0.999999 mol) to astoichiometric amount (1 mol), or an excess amount (more than 1 and1,000,000 mol or less) relative to 1 mol of the reactant7-methyl-3-methylene-7-octenal (2). It is preferably the catalyticamount to 200 mol relative to 1 mol of the reactant7-methyl-3-methylene-7-octenal (2).

The solvent to be used in the isomerization in the presence of the basemay be the above base which will be used as it is, or may be a singlesolvent or mixed solvent of two or more solvents selected from water;alcohols such as methanol, ethanol and n-propanol; chlorinated solventssuch as methylene chloride, chloroform and trichloroethylene;hydrocarbons such as hexane, heptane, benzene, toluene, xylene andcumene; ethers such as diethyl ether, dibutyl ether, diethylene glycoldiethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran and1,4-dioxane; nitriles such as acetonitrile; ketones such as acetone and2-butanone; esters such as ethyl acetate and n-butyl acetate; andaprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxideand hexamethylphosphoric triamide.

The reaction temperature of the isomerization may be appropriatelyselected depending on a type of the base to be used and reactionconditions. Typically, it is preferably −50° C. to the boiling point ofthe solvent, more preferably −20° C. to room temperature. The geometricisomer ratio of target compounds (5), in other words, the ratio of (5z)to (5e) varies depending on a type or amount of the base to be used andreaction conditions, so that an appropriate reagent and conditions maybe selected in consideration of the geometric isomer ratio.

The reaction time of the isomerization may be freely selected. Theconversion and the isomer ratio may be optimized by monitoring thereaction by means of gas chromatography (GC) or thin-layerchromatography (TLC). Typically, the reaction time is preferably 5minutes to 240 hours.

When the 3,7-dimethyl-2,7-octadienal (5) or the mixture of7-methyl-3-methylene-7-octenal (2) and 3,7-dimethyl-2,7-octadienal (5)produced by the above isomerization has a sufficient purity or aintended isomer ratio, the crude product may be subjected to the nextstep directly, or may be subjected to purification or isomer separationby a method appropriately selected from purification methods and isomerseparation methods commonly used in organic syntheses, such asdistillation and various types of chromatography. The distillation isparticularly preferable from the standpoint of industrial economy.

[7] Method for Producing 3,7-dimethyl-2,7-octadienol (6)

The formyl group of the 3,7-dimethyl-2,7-octadienal (5) produce abovemay be reduced to obtain a corresponding 3,7-dimethyl-2,7-octadienol(6).

The reduction conditions are the same as those for the method forproducing 7-methyl-3-methylene-7-octenol (3).

The reducing agent or the reaction conditions are preferably selected soas to avoid reduction of the double bonds of 3,7-dimethyl-2,7-octadienal(5). In the reduction of 3,7-dimethyl-2,7-octadienal (5) to3,7-dimethyl-2,7-octadienol (6), it is preferable to select such areducing agent or reaction conditions as to produce a target compound3,7-dimethyl-2,7-octadienol (6) by 1,2-reduction, while suppressing anamount of the by-product 3,7-dimethyl-7-octenol by 1,4-reduction.

When the 3,7-dimethyl-2,7-octadienol (6) produced by the above reductionhas a sufficient purity or an intended isomer ratio, the crude productmay be subjected to the next step directly, or may be subjected topurification or isomer separation by a method appropriately selectedfrom purification methods and isomer separation methods commonly used inorganic syntheses, such as distillation and various types ofchromatography. The distillation is particularly preferable from thestandpoint of industrial economy.

[8] Method for Producing 3,7-dimethyl-2,7-octadienyl carboxylateCompound (7)

The alcohol compound 3,7-dimethyl-2,7-octadienol (6) produced above isesterified to obtain a corresponding 3,7-dimethyl-2,7-octadienylcarboxylate compound (7).

R³ is a hydrogen atom or a monovalent hydrocarbon group having 1 to 6carbon atoms. Examples of the monovalent hydrocarbon group having 1 to 6carbon atoms include those described in the method for producing a7-methyl-3-methylene-7-octenyl carboxylate compound (4).

The esterification conditions are the same as those described in themethod for producing a 7-methyl-3-methylene-7-octenyl carboxylatecompound (4).

The 3,7-dimethyl-2,7-octadienyl carboxylate compound (7) produced abovemay be purified by a method appropriately selected from purificationmethods commonly used in organic syntheses, such as distillation underreduced pressure and various types of chromatography. The distillationunder reduced pressure is preferable from the standpoint of industrialeconomy.

[9] Method for Simultaneously Producing 7-methyl-3-methylene-7-octenol(3) and 3,7-dimethyl-2,7-octadienol (6)

The formyl groups of the mixture of 7-methyl-3-methylene-7-octenal (2)and 3,7-dimethyl-2,7-octadienal (5) produced above may be reduced toobtain a corresponding mixture of 7-methyl-3-methylene-7-octenol (3) and3,7-dimethyl-2,7-octadienol (6).

The reduction conditions are the same as those for the method forproducing 7-methyl-3-methylene-7-octenol (3).

The reducing agent or the reaction conditions are preferably selected soas to avoid reduction of the double bonds of 3,7-dimethyl-2,7-octadienal(5). For the reduction of 3,7-dimethyl-2,7-octadienal (5) to3,7-dimethyl-2,7-octadienol (6), it is preferable to select such areducing agent or reaction conditions as to produce a target compound3,7-dimethyl-2,7-octadienol (6) by 1,2-reduction, while suppressing anamount of the by-product 3,7-dimethyl-7-octenol by 1,4-reduction.

When a mixture of 7-methyl-3-methylene-7-octenol (3) and3,7-dimethyl-2,7-octadienol (6) produced by the above reduction has asufficient purity or an intended isomer ratio, the crude product may besubjected to the next step directly, or may be subjected to purificationor isomer separation by a method appropriately selected frompurification methods and isomer separation methods commonly used in theorganic syntheses, such as distillation and various types ofchromatography. The distillation is particularly preferable from thestandpoint of industrial economy.

[10] Method for Simultaneously Producing 7-methyl-3-methylene-7-octenylcarboxylate Compound (4) and 3,7-dimethyl-2,7-octadienyl carboxylateCompound (7)

The mixture of 7-methyl-3-methylene-7-octenol (3) and3,7-dimethyl-2,7-octadienol (6) produced above may be esterified toobtain a corresponding mixture of a 7-methyl-3-methylene-7-octenylcarboxylate compound (4) and a 3,7-dimethyl-2,7-octadienyl carboxylatecompound (7).

R³ is a hydrogen atom or a monovalent hydrocarbon group having 1 to 6carbon atoms. Examples of the monovalent hydrocarbon group having 1 to 6carbon atoms include those described in the method for producing a7-methyl-3-methylene-7-octenyl carboxylate compound (4).

The esterification conditions are the same as those described in themethod for producing a 7-methyl-3-methylene-7-octenyl carboxylatecompound (4).

The mixture of a 7-methyl-3-methylene-7-octenyl carboxylate compound (4)and a 3,7-dimethyl-2,7-octadienyl carboxylate compound (7) produced bythe above esterification may be subjected to purification or isomerseparation by a method appropriately selected from purification methodsand isomer separation methods commonly used in organic syntheses, suchas distillation and various types of chromatography. The distillation isparticularly preferable from the standpoint of industrial economy.

As described above, the 7-methyl-3-methylene-7-octenal acetal compoundmay be used as a common intermediate to efficiently produce the7-methyl-3-methylene-7-octenal, the 7-methyl-3-methylene-7-octenylcarboxylate compound, the 3,7-dimethyl-2,7-octadienal, the3,7-dimethyl-2,7-octadienyl carboxylate compound, and the mixture of the7-methyl-3-methylene-7-octenyl carboxylate compound and the3,7-dimethyl-2,7-octadienyl carboxylate compound.

EXAMPLES

The invention will next be described in further detail with reference toExamples. It should not be construed that the invention is limited to orby Examples.

The purities of raw materials, products and intermediates are determinedby gas chromatographic (GC) analyses and are expressed with % GC. Theisomer ratio of products or intermediates is expressed as an area ratioby GC analysis. GC conditions

GC: Shimazdu GC-14A,

Column: 5% Ph-Me silicone, 0.25 mmϕ×25 m,

Carrier gas: He, and

Detector: FID.

The yield is the conversion yield based on % GC. Materials to be used ina reaction and products produced by the reaction are not always 100%pure, so that the conversion yield (%) is calculated in accordance with100×[{(weight of product obtained by reaction)×(% GC)}/(molecular weightof product)]/[{(weight of starting material in reaction)×(%GC)}/(molecular weight of starting material)]. The detection sensitivityof gas chromatography varies with compounds, so that the conversionyield may exceed 100% especially when a material or a product is crude.

A compound sample for spectrum measurement was prepared by optionalpurification of a crude product.

Example 1: Production of 3-acetoxymethyl-3-butenal diethyl acetal[R¹═R²═CH₂CH₃=Et, X¹═OCOCH₃═OAc in General Formula (10)]

Under a nitrogen atmosphere, a mixture of 94.0 g of3-bromomethyl-3-butenal diethyl acetal, 100 g of sodium acetate and1,000 ml of N,N-dimethylacetamide was stirred at 100 to 120° C. for 2hours. After cooled, the reaction mixture was poured in a saturatedaqueous sodium hydrogen carbonate solution and extracted with n-hexane.The organic phase was subjected to common work-up of washing, drying andconcentration to obtain 63.6 g of crude 3-acetoxymethyl-3-butenaldiethyl acetal (1) (63.4% GC, yield: 47%). A part of the crude productwas distilled under reduced pressure to obtain a sample (86.5% GC) forspectrum measurement.

3-Acetoxymethyl-3-butenal diethyl acetal

Colorless oil.

Boiling point: 69° C./399 Pa.

IR (D-ATR): ν=2976, 2931, 2879, 1743, 1652, 1444, 1373, 1230, 1126, 1058cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.18 (6H, t, J=7.1 Hz), 2.07 (3H, s), 2.38(2H, d, J=5.7 Hz), 3.45-3.52 (2H, m), 3.60-3.68 (2H, m), 4.55 (2H, s),4.58 (1H, t, J=5.7 Hz), 5.04 (1H, br. s), 5.10 (1H, br. s) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=15.19 (2C), 20.87, 37.81, 61.41 (2C), 67.04,102.02, 114.84, 139.65, 170.58 ppm.

GC-MS (EI, 70 eV): 29, 47, 61, 75, 103 (base peak), 127, 171, 215[(M-H)⁺].

Example 2: Production of 3-acetoxymethyl-3-butenal dibutyl acetal[R¹═R²═CH₂CH₂CH₂CH₃=Bu, X¹═OCOCH₃═OAc in General Formula (10)]

In the same manner as in Example 1 except that 9.10 g of3-bromomethyl-3-butenal dibutyl acetal (82.0% GC) was used in place of3-bromomethyl-3-butenal diethyl acetal, 4.85 g of crude3-acetoxymethyl-3-butenal dibutyl acetal (70.0% GC, yield: 70%) wasproduced. A part of the crude product was purified by silica gel columnchromatography to obtain a sample (90.5% GC) for spectrum measurement.

3-Acetoxymethyl-3-butenal dibutyl acetal

Colorless oil.

IR (D-ATR): ν=2959, 2934, 2873, 1745, 1653, 1460, 1374, 1229, 1116,1071, 1046 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=0.90 (6H, t, J=7.3 Hz), 1.32-1.40 (2H, m),1.50-1.57 (2H, m), 2.07 (3H, s), 2.38 (2H, d, J=5.8 Hz), 3.39-3.44 (2H,m), 3.56-3.60 (2H, m), 4.55 (2H, s), 4.56 (1H, t, J=5.8 Hz), 5.03 (1H,br. s), 5.10 (1H, br. s) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=13.83 (2C), 19.36 (2C), 20.88, 31.86 (2C),37.70, 65.70 (2C), 67.09, 102.24, 114.80, 139.71, 170.58 ppm.

GC-MS (EI, 70 eV): 43, 57 (base peak), 83, 103, 159, 199, 271 [(M-H)⁺].

Example 3: Production No. 1 of 7-methyl-3-methylene-7-octenal diethylacetal [R¹═R²═CH₂CH₃=Et in General Formula (1)]

Under a nitrogen atmosphere, a mixture of 32.1 g of3-bromomethyl-3-butenal diethyl acetal which had been produced fromethyl 3,3-diethoxypropionate as a starting material in accordance with amethod described in I. V. Mineeva et al., Russian Journal of OrganicChemistry, 45, 1623 (2009), 30 mg of copper(I) iodide, 45 mg oftriethylphosphite and 200 ml of tetrahydrofuran was stirred on ice. Themixture was subjected to dropwise addition, at 15° C. or less over 40minutes, of 250 ml of a 0.75M 3-methyl-3-butenyl magnesium bromidesolution in tetrahydrofuran which had been produced as the Grignardreagent from 3-methyl-3-butenyl bromide, 3.10 g of 1,2-dibromoethane,4.44 g of magnesium and 220 ml of tetrahydrofuran by a common method.The reaction mixture was stirred on ice for 100 minutes. Then themixture was subjected to addition of a saturated aqueous ammoniumchloride solution, and extracted with ethyl acetate. The separatedorganic phase was subjected to common work-up of washing, drying andconcentration to obtain a crude product. The crude product was distilledunder reduced pressure to obtain 18.38 g of7-methyl-3-methylene-7-octenal diethyl acetal (93% GC, yield: 74%).

7-Methyl-3-methylene-7-octenal diethyl acetal

Colorless oil.

Boiling point: 71-74° C./266 Pa.

IR (D-ATR): ν=3074, 2975, 2932, 1648, 1444, 1372, 1128, 1061, 1023, 888cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.19 (6H, t, J=7 Hz), 1.54-1.60 (2H, m), 1.70(3H, s), 2.00 (2H, t, J=7.6 Hz), 2.05 (2H, t, J=7.6 Hz), 2.34 (2H, d,J=5.7 Hz), 3.46-3.54 (2H, m), 3.61-3.68 (2H, m), 4.61 (1H, t, J=5.7 Hz),4.66 (1H, br. s), 4.69 (1H, br. s), 4.82-4.83 (2H, m) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=15.24 (2C), 22.35, 25.52, 36.09, 37.37,40.19, 61.00 (2C), 102.07, 109.86, 111.68, 145.20, 145.77 ppm.

GC-MS (EI, 70 eV): 29, 47, 75, 103 (base peak), 119, 135, 225 [(M-H)⁺].

Example 4: Production No. 2 of 7-methyl-3-methylene-7-octenal diethylacetal [R¹═R²═CH₂CH₃=Et in General Formula (1)]

In the same manner as in Example 3 except that 10.0 g of3-acetoxymethyl-3-butenal diethyl acetal (86.5% GC) was used in place of3-bromomethyl-3-butenal diethyl acetal, 12.37 g of7-methyl-3-methylene-7-octenal diethyl acetal (80.8% GC, quantitativeyield) was produced. The obtained target compound was identical with thetarget compound in Example 3.

Example 5: Production of 7-methyl-3-methylene-7-octenal dibutyl acetal[R¹═R²═CH₂CH₂CH₂CH₃=Bu in General Formula (1)]

In the same manner as in Example 3 except that 0.65 g of3-acetoxymethyl-3-butenal dibutyl acetal (90.5% GC) was used in place of3-bromomethyl-3-butenal diethyl acetal, 0.81 g of7-methyl-3-methylene-7-octenal dibutyl acetal (82.3% GC, quantitativeyield) was produced.

7-Methyl-3-methylene-7-octenal dibutyl acetal

Colorless oil.

IR (D-ATR): ν=2959, 2934, 2872, 1649, 1456, 1375, 1232, 1116, 1072, 1039cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=0.91 (6H, t, J=7.3 Hz), 1.33-1.42 (4H, m),1.51-1.60 (6H, m), 1.71 (3H, s), 2.00 (2H, br. t, J=7.6 Hz), 2.05 (2H,br. t, J=7.7 Hz), 2.34 (2H, d, J=5.7 Hz), 3.39-3.44 (2H, m), 3.56-3.61(2H, m), 4.58 (1H, t, J=5.7 Hz), 4.67 (1H, br. s), 4.70 (1H, br. s) 4.81(1H, br. s), 4.82 (1H, br. s) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=13.88 (2C), 19.40 (2C), 22.35, 25.56, 31.93(2C), 36.12, 37.40, 40.11, 65.34 (2C), 102.35, 109.85, 111.63, 145.29,145.80 ppm.

GC-MS (EI, 70 eV): 41, 57 (base peak), 81, 103, 121, 135, 159, 281[(M-H)⁺].

Example 6: Production of 7-methyl-3-methylene-7-octenal dimethyl acetal[R¹═R²═CH₃=Me in General Formula (1)]

Under a nitrogen atmosphere, a mixture of 2.0 g of7-methyl-3-methylene-7-octenal diethyl acetal (83.6% GC), 15.0 g ofmethanol and 0.05 g of pyridinium p-toluenesulfonate monohydrate wasstirred at room temperature for 2 hours. The reaction mixture was pouredin a saturated aqueous sodium hydrogen carbonate solution and extractedwith n-hexane. The separated organic phase was subjected to commonwork-up of washing, drying and concentration to obtain 0.91 g of7-methyl-3-methylene-7-octenal dimethyl acetal (86.6% GC, yield: 54%).

7-Methyl-3-methylene-7-octenal dimethyl acetal

Colorless oil.

IR (D-ATR): ν=3074, 2936, 2830, 1648, 1446, 1373, 1192, 1123, 1078,1060, 888 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.55-1.61 (2H, m), 1.71 (3H, s), 2.01 (2H, t,J=7.6 Hz), 2.05 (2H, t, J=7.8 Hz), 2.34 (2H, d, J=5.7 Hz), 3.32 (6H, s),4.51 (1H, t, J=5.8 Hz), 4.67 (1H, br. s), 4.70 (1H, br. s), 4.79 (2H,br. s) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=22.35, 25.53, 35.89, 37.34, 39.20, 52.70(2C), 103.41, 109.91, 111.86, 144.88, 145.73 ppm.

GC-MS (EI, 70 eV): 47, 75 (base peak), 109, 197 [(M-H)⁺].

Example 7: Production of 7-methyl-3-methylene-7-octenal ethylene acetal[R¹—R²═CH₂CH₂ in General Formula (1)]

Under a nitrogen atmosphere, a mixture of 3.0 g of7-methyl-3-methylene-7-octenal diethyl acetal (83.6% GC), 4.00 g ofethylene glycol, 0.05 g of pyridinium p-toluenesulfonate monohydrate and12 ml of toluene was stirred and refluxed with heating, while distillingoff the generated ethanol. Two hours later when the distillation wasover, the reaction mixture was cooled to room temperature, then pouredin water, and extracted with n-hexane. The separated organic phase wassubjected to common work-up of washing, drying and concentration toobtain 2.61 g of 7-methyl-3-methylene-7-octenal ethylene acetal (83.4%GC, quantitative yield).

7-Methyl-3-methylene-7-octenal ethylene acetal

Colorless oil.

IR (D-ATR): ν=3074, 2936, 2883, 1648, 1444, 1396, 1213, 1133, 1044, 889cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.55-1.62 (2H, m), 1.71 (3H, s), 2.01 (2H, t,J=7.6 Hz), 2.08 (2H, t, J=7.8 Hz), 2.38 (2H, d, J=5.2 Hz), 3.82-3.88(2H, m), 3.94-4.01 (2H, m), 4.67 (1H, br. s-like), 4.70 (1H, br.s-like), 4.88 (2H, br. s-like), 4.97 (1H, t, J=5.2 Hz) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=22.33, 25.47, 36.09, 37.31, 40.63, 64.76(2C), 103.60, 109.88, 112.22, 144.48, 145.70 ppm.

GC-MS (EI, 70 eV): 45, 73 (base peak), 195 [(M-H)⁺].

Example 8: Production No. 1 of 7-methyl-3-methylene-7-octenal (2)

Under a nitrogen atmosphere, 2.00 g of 7-methyl-3-methylene-7-octenaldiethyl acetal (93% GC) and 6.00 g of a mixture of water, acetic acidand formic acid at a weight ratio of 10:5:1 were stirred at 50° C. for 1hour and at 60° C. for 4 hours. The reaction mixture was cooled anddiluted with toluene. The separated organic phase was subjected tocommon work-up of washing, drying and concentration to obtain, as acrude product, 1.58 g of a mixture (65% GC, total yield of threecompounds: 77%) of 7-methyl-3-methylene-7-octenal,Z-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at a¹H-NMR integral area ratio of 80.9:7.6:11.5.

7-Methyl-3-methylene-7-octenal

Yellowish liquid

IR (D-ATR): ν=3075, 2970, 2937, 1725, 1675, 1647, 1445, 1375, 890 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.55-1.63 (2H, m), 1.71 (3H, s), 2.01 (2H, t,J=7.7 Hz), 2.06 (2H, t, J=7.7 Hz), 3.09 (2H, d-like, J=2.7 Hz), 4.68(1H, br. s), 4.2 (1H, br. s), 4.92 (1H, br. s), 5.05 (1H, br. s), 9.64(1H, t, J=2.7 Hz) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=22.26, 25.09, 36.19, 37.11, 50.95, 110.17,114.78, 140.54, 145.28, 199.99 ppm.

GC-MS (EI, 70 eV): 41 (base peak), 53, 67, 81, 93, 108, 119, 137, 152(M⁺).

Example 9: Production No. 2 of 7-methyl-3-methylene-7-octenal (2)

Under a nitrogen atmosphere, a mixture of 20.0 g of7-methyl-3-methylene-7-octenal diethyl acetal (83% GC), 10 ml oftetrahydrofuran and 10 ml of toluene was subjected to addition of 50 gof 10% hydrochloric acid, and stirred at room temperature for 8 hoursand at 40° C. for 1 hour. The reaction mixture was cooled, and then theorganic phase was separated. The organic phase having a reactionconversion [=100×(product GC %)/{(product GC %+material GC %)}] of 70%contained 7-methyl-3-methylene-7-octenal, Z-3,7-dimethyl-2,7-octadienaland E-3,7-dimethyl-2,7-octadienal at a GC % ratio of 82.8:7.3:9.9. Theorganic phase was not further purified and was subjected to the nextstep.

Example 10: Production No. 3 of 7-methyl-3-methylene-7-octenal (2)

Under a nitrogen atmosphere, a mixture of 0.50 g of7-methyl-3-methylene-7-octenal dimethyl acetal (87% GC), 1.8 g of oxalicacid dihydrate, 2 ml of tetrahydrofuran and 4 ml of water was stirred atroom temperature for 6 hours. The reaction mixture was cooled and thendiluted with n-hexane. The separated organic phase was subjected tocommon work-up of washing, drying and concentration to obtain, as acrude product, 0.24 g of a mixture (87.7% GC, total yield of threecompounds: 66%) of 7-methyl-3-methylene-7-octenal,Z-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at a GC% ratio of 83.1:6.6:10.3. The obtained target compound was identicalwith the target compound in Example 8.

Example 11: Production of 7-methyl-3-methylene-7-octenol (3)

Under a nitrogen atmosphere, a mixture of 3.50 g of sodium borohydride,2 ml of a 20% aqueous sodium hydroxide solution and 60 ml of water wascooled on ice and subjected to dropwise addition, at 10° C. or less over20 minutes, of the organic phase containing7-methyl-3-methylene-7-octenal (2) and being obtained in Example 9. Thereaction mixture was stirred for 24 hours, and then the organic phasewas separated. The separated organic phase was subjected to commonwork-up of washing, drying and concentration to obtain 13.45 g of acrude product. The crude product contained 49.1% GC (conversion yield:49%) of the target compound 7-methyl-3-methylene-7-octenol and 24.8% GC(converted yield: 20.3%) of 7-methyl-3-methylene-7-octenal diethylacetal, which was the starting material in Example 9. The crude productwas separated and purified by silica gel column chromatography to obtain3.66 g of the starting material 7-methyl-3-methylene-7-octenal diethylacetal (83.1% GC, 2-step recovery yield from Example 9: 18%) and twofractions: 5.00 g (97.7% GC) and 0.84 g (95.2% GC) of the targetcompound 7-methyl-3-methylene-7-octenol. The 2-step yield of the totalof the two fractions of 7-methyl-3-methylene-7-octenol was 54% fromExample 9, and the 2-step yield of 7-methyl-3-methylene-7-octenol inconsideration of material recovery was 66% from Example 9.

7-Methyl-3-methylene-7-octenol

Yellowish oil

IR (D-ATR): ν=3336, 3074, 2936, 1647, 1445, 1374, 1046, 887 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.54-1.64 (2H, m), 1.63 (1H, OH, t-like,J=ca. 5 Hz), 1.71 (3H, s), 1.97-2.07 (4H, m), 2.29 (2H, t-like, J=6.4Hz), 3.70 (2H, q-like, J=ca. 6 Hz), 4.67 (1H, br. s), 4.70 (1H, br. s),4.82 (1H, br. s), 4.86 (1H, br. s) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=22.31, 25.53, 35.26, 37.30, 39.09, 60.31,109.97, 111.59, 145.59, 145.91 ppm.

GC-MS (EI, 70 eV): 41, 55, 68 (base peak), 81, 93, 109, 121, 139, 154(M⁺).

GC-MS (CI, isobutane): 69, 81, 95, 111, 125, 137, 155 [(M+H)⁺].

Example 12: Production of 7-methyl-3-methylene-7-octenyl propionate[R³═CH₂CH₃ in General Formula (4)]

Under a nitrogen atmosphere, a mixture of 5.45 g of7-methyl-3-methylene-7-octenol (88.3% GC), 10.0 g of pyridine and 30 mlof tetrahydrofuran was subjected to addition of 4.80 g of propionicanhydride. The reaction mixture was refluxed with heating and stirringfor 5 hours, and then subjected to addition of a saturated aqueoussodium hydrogen carbonate solution to stop the reaction. The separatedorganic phase was subjected to common work-up of washing, drying andconcentration to obtain 7.44 g of a crude product of7-methyl-3-methylene-7-octenyl propionate. The crude product wasdistilled under reduced pressure to obtain 5.25 g of the target compound7-methyl-3-methylene-7-octenyl propionate (95.5% GC, yield includinginitial distillate having 87.7% GC: 91%).

7-Methyl-3-methylene-7-octenyl propionate

Colorless oil

Boiling point: 80° C./399 Pa.

IR (D-ATR): ν=3076, 2981, 2938, 1739, 1648, 1462, 1376, 1349, 1273,1181, 1084, 1016, 889 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.12 (3H, t, J=7.6 Hz), 1.53-1.61 (2H, m),1.71 (3H, s), 1.97-2.06 (4H, m), 2.31 (2H, q, J=7.6 Hz), 2.33 (2H,t-like, J=7 Hz), 4.17 (2H, t, J=7.1 Hz), 4.67 (1H, s- like), 4.70 (1H,s-like), 4.77 (1H, s-like), 4.81 (1H, s-like) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=9.10, 22.32, 25.51, 27.56, 34.95, 35.86,37.29, 62.73, 109.96, 111.18, 145.44, 145.60, 174.41 ppm.

GC-MS (EI, 70 eV): 29, 41, 57 (base peak), 68, 79, 93, 107, 121, 136,210 (M⁺).

Example 13: Production of 7-methyl-3-methylene-7-octenyl senecioate[R³═CH:C(CH₃)₂ in General Formula (4)]

Under a nitrogen atmosphere, a mixture of 4.00 g of7-methyl-3-methylene-7-octenol (95.2% GC), 10.0 g of methyl senecioateand 0.5 ml of titanium(IV) isopropoxide was heated, while graduallyincreasing the bath temperature from 80° C. to 155° C. and distillingoff the generated methanol. Two hours later when the distillation ofmethanol was over as a result of continuous heating, the vaportemperature increased to 136° C., which was the boiling point of methylsenecioate. The reaction mixture was cooled, and then was directlydistilled under reduced pressure to recover excess methyl senecioate.Then 2.89 g of the target compound 7-methyl-3-methylene-7-octenylsenecioate (96.6% GC, yield including initial distillate having 84.7%GC: 56%) was obtained.

7-Methyl-3-methylene-7-octenyl senecioate

Colorless oil

Boiling point: 94-95° C./399 Pa.

IR (D-ATR): ν=3075, 2969, 2937, 2916, 1720, 1651, 1446, 1377, 1348,1272, 1228, 1147, 1080, 1000, 889, 851 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.54-1.61 (2H, m), 1.70 (3H, s), 1.88 (3H, d,J=1.3 Hz), 2.02 (4H, quint-like, J=ca. 7 Hz), 2.15 (3H, d, J=1.1 Hz),2.35 (2H, t-like, J=7 Hz), 4.19 (2H, t, J=7.1 Hz), 4.66 (1H, s-like),4.70 (1H, s-like), 4.79 (1H, s-like), 4.81 (1H, s-like), 5.66 (1H,septet, J=1.3 Hz) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=20.14, 22.32, 25.52, 27.33, 35.01, 35.69,37.30, 62.02, 109.94, 111.07, 115.99, 145.61, 145.63, 156.54, 166.61ppm.

GC-MS (EI, 70 eV): 29, 41, 55, 68, 83 (base peak), 95, 107, 121, 136,236 (M⁺).

Example 14: Production of 7-methyl-3-methylene-7-octenyl acetate [R³═CH₃in General Formula (4)]

Under a nitrogen atmosphere, a mixture of 5.00 g of7-methyl-3-methylene-7-octenol (95.2% GC), 10.0 g of pyridine and 4.00 gof acetic anhydride was stirred at room temperature for 3 hours. Thereaction mixture was poured in cold water and extracted with diethylether. The crude product obtained by common washing, drying andconcentration was distilled under reduced pressure to obtain 5.82 g ofthe target compound 7-methyl-3-methylene-7-octenyl acetate (96.4% GC,yield including initial distillate having 91.9% GC: 96%).

7-Methyl-3-methylene-7-octenyl acetate

Colorless oil

Boiling point: 56-58° C./399 Pa.

IR (D-ATR): ν=3075, 2967, 2937, 2866, 1743, 1648, 1445, 1365, 1237,1036, 889 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.53-1.60 (2H, m), 1.98-2.04 (4H, m), 2.03(3H, s), 2.33 (2H, t-like, J=7.1 Hz), 4.16 (2H, t, J=7.1 Hz), 4.66 (1H,s-like), 4.70 (1H, s-like), 4.77 (1H, s-like), 4.81 (1H, s-like) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=20.93, 22.32, 25.48, 34.86, 35.65, 37.28,62.88, 109.97, 111.17, 145.38, 145.58, 171.02 ppm.

GC-MS (EI, 70 eV): 29, 43 (base peak), 56, 69, 81, 95, 109, 124, 137.

Example 15: Production No. 1 of 3,7-dimethyl-2,7-octadienal (5)

Under a nitrogen atmosphere, a mixture of 1.00 g of pyridine and 5.00 gof toluene with 1.00 g of a mixture (65.6% GC, containing 37.3% toluene)of 7-methyl-3-methylene-7-octenal, Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a ratio of 76:9:16 was refluxed withheating and stirring for 8 hours. The reaction mixture was cooled, thenpoured in a diluted hydrochloric acid, and extracted with n-hexane. Theorganic phase was subjected to common work-up of washing, drying andconcentration to obtain, as a crude product, 0.80 g of a mixture (86.2%GC, quantitative yield) of Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a ratio of 35:65.

3,7-Dimethyl-2,7-octadienal

Isomer ratio Z:E=35.0:65.0

Yellowish oil

IR (D-ATR): ν=3074, 2938, 2861, 1675, 1444, 1376, 1195, 1122, 887 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.62-1.69 (2H, m, Z & E), 1.70 (3H, s-like, Z& E), 1.96 (3×0.35H, d, J=1.2 Hz, Z), 2.00-2.06 (2H, m, Z & E), 2.15(3×0.65H, d, J=1.2 Hz, E), 2.19 (2×0.65H, br. t, J=7.7 Hz, E), 2.55(2×0.35H, dd, J=7.6, 8.1 Hz, Z), 4.66-4.74 (2H, m, Z & E), 5.86-5.88(2H, m, Z & E), 9.93 (0.35H, d, J=8 Hz, Z), 9.84 (0.65H, d, J=8 Hz, E)ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=17.47 (Z & E), 22.19 (Z & E), 24.85 (E),26.33 (Z), 31.89 (Z), 37.04 (E), 37.13 (Z), 39.94 (E), 110.50 (E),110.69 (Z), 127.34 (E), 128.53 (Z), 144.56 (E), 144.79 (Z), 163.94 (E),164.34 (Z), 190.67 (Z), 191.22 (E) ppm.

GC-MS (EI, 70 eV): (Z)-isomer: 41, 53, 67, 84 (base peak), 95, 109, 119,137, 152 (M⁺); (E)-isomer: 41 (base peak), 53, 67, 81, 95, 109, 123,137, 152 (M⁺).

GC-MS (CI, isobutane): (Z)-isomer: 71, 95, 109 (base peak), 135, 153[(M+H)⁺]; (E)-isomer: 71, 95, 109 (base peak), 135, 153 [(M+H)⁺].

Example 16: Production No. 2 of 3,7-dimethyl-2,7-octadienal (5)

Under a nitrogen atmosphere, a mixture of 2.00 g of1,8-diazabicyclo[5.4.0]-7-undecene and 80 ml of toluene with 62.3 g of amixture (52.4% GC, containing 37.1% toluene) of7-methyl-3-methylene-7-octenal, Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a ratio of 39:23:38 was stirred at roomtemperature for 3 hours. The reaction mixture contained a mixture ofZ-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at aratio of 37:63. Components of the reaction mixture were identical withthose in Example 15 except for the isomer ratio.

Example 17: Production No. 3 of 3,7-dimethyl-2,7-octadienal (5)

Under a nitrogen atmosphere, a mixture of 0.1 g of triethylamine and 1ml of tetrahydrofuran with 200 mg of a mixture (87.3% GC) of7-methyl-3-methylene-7-octenal, Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a GC % ratio of 55:16:29 was stirred atroom temperature for 18 hours. The reaction mixture contained a mixtureof Z-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at aratio of 18:82. Components of the reaction mixture were identical withthose in Example 15 except for the isomer ratio.

Example 18: Production No. 4 of 3,7-dimethyl-2,7-octadienal (5)

Under a nitrogen atmosphere, a mixture of 2.0 g of triethylamine and 100ml of tetrahydrofuran with 28.5 g of a mixture (87.3% GC) of7-methyl-3-methylene-7-octenal, Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a ratio of 55:16:29 was stirred at roomtemperature for 18 hours. The reaction mixture contained a mixture ofZ-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at aratio of 19:81. Components of the reaction mixture were identical withthose in Example 15 except for the isomer ratio.

Example 19: Production No. 1 of 3,7-dimethyl-2,7-octadienol (6)

Under a nitrogen atmosphere, a mixture of 22.0 g of sodium borohydride,10 ml of a 15% aqueous sodium hydroxide solution and 300 ml of water wasstirred on ice, and a mixture of 500 ml of tetrahydrofuran with 128.4 gof a mixture (68.9% GC) of Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a ratio of 36:64 was added dropwise at12° C. or less over 1 hour. The reaction mixture was stirred on ice for40 minutes and at room temperature for 1 hour. Then the organic phasewas separated, and the aqueous phase was extracted with diethyl ether.The combined organic phase was subjected to common work-up of washing,drying and concentration to obtain a crude product. The crude productwas a mixture (74.8% GC, quantitative yield) ofZ-3,7-dimethyl-2,7-octadienol and E-3,7-dimethyl-2,7-octadienol at aratio of 33:67. The crude product was not further purified and wassubjected to the next step.

3,7-Dimethyl-2,7-octadienol

Isomer ratio Z:E=33:67.

Yellowish oil

IR (D-ATR): ν=3336, 3074, 2968, 2935, 1649, 1444, 1375, 999, 886 cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.45 (1H, br, Z & E), 1.48-1.59 (2H, m, Z &E), 1.66 (3×0.64H, br. s, E), 1.70 (3H, br. s, Z & E), 1.73 (3 x 0.33H,br. s, Z), 1.95-2.03 (4×0.67H+2×0.33H, m, Z & E), 2.06 (2×0.33H, br. t,J=8 Hz, Z), 4.10 (0.33H, br. s, Z), 4.11 (0.33H, br. s, Z), 4.13 (0.67H,br. s, E), 4.15 (0.67H, br. s, E), 4.63-4.74 (2H, m, Z & E), 5.38-5.44(1H, m, Z & E) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=16.13 (E), 22.34 (E+Z), 23.34 (Z), 25.53(E), 25.99 (Z), 31.38 (Z), 37.29 (E), 37.39 (Z), 39.04 (E), 58.97 (Z),59.29 (E), 109.86 (E), 109.95 (Z), 123.39 (E), 124.27 (Z), 139.62 (E),139.95 (Z), 145.55 (Z), 145.71 (E) ppm.

GC-MS (EI, 70 eV): (Z)-isomer: 41, 55, 69 (base peak), 83, 96, 109, 121,136, 154 (M⁺); (E)-isomer: 41, 55, 69 (base peak), 83, 96, 109, 121,136, 154 (M⁺).

Example 20: Production No. 2 of 3,7-dimethyl-2,7-octadienol (6)

Under a nitrogen atmosphere, a mixture of 5.0 g of sodium borohydride,5.0 g of a 20% aqueous sodium hydroxide solution and 50 ml of water wasstirred on ice, and a mixture of 100 ml of ethanol with the reactionmixture containing Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a ratio of 37:63 and being obtained inExample 16 was dropwise added thereto over 20 minutes. The reactionmixture was stirred at room temperature for 16 hours, then the organicphase was separated, and the aqueous phase was extracted with diethylether. The combined organic phase was subjected to common work-up ofwashing, drying and concentration to obtain a crude product. The crudeproduct was a mixture (69.2% GC, quantitative yield) ofZ-3,7-dimethyl-2,7-octadienol and E-3,7-dimethyl-2,7-octadienol at aratio of 37:63. Components of the mixture were identical with those inExample 19 except for the isomer ratio.

Example 21: Production No. 3 of 3,7-dimethyl-2,7-octadienol (6)

Under a nitrogen atmosphere, the reaction mixture containingZ-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at aratio of 19:81 and being obtained in Example 18 was stirred on ice, anda mixture of 5.0 g of sodium borohydride, 0.4 ml of a 20% aqueous sodiumhydroxide solution and 100 ml of water was dropwise added thereto at 12°C. or less over 20 minutes. The reaction mixture was stirred on ice for140 minutes, then a saturated salt solution was added thereto, and theorganic phase was separated. The organic phase was subjected to commonwork-up of washing, drying and concentration to obtain a crude product.The crude product was a mixture (78.8% GC, yield: 94%) ofZ-3,7-dimethyl-2,7-octadienol and E-3,7-dimethyl-2,7-octadienol at aratio of 19:81. Components of the mixture were identical with those inExample 19 except for the isomer ratio.

Example 22: Production No. 1 of 3,7-dimethyl-2,7-octadienyl propionate[R³═CH₂CH₃ in General Formula (7)]

Under a nitrogen atmosphere, a mixture of 90.0 g of pyridine and 700 mlof t-butyl methyl ether with 122 g of the mixture (74.8% GC) ofZ-3,7-dimethyl-2,7-octadienol and E-3,7-dimethyl-2,7-octadienol at aratio of 33:67 obtained in Example 19 was stirred on ice, and 55.0 g ofpropionyl chloride was dropwise added thereto at 12° C. or less over 50minutes. The reaction mixture was stirred at room temperature for 14hours, then cooled on ice, and a saturated aqueous sodium hydrogencarbonate solution was added thereto. The separated organic phase wassubjected to common work-up of washing, drying and concentration toobtain 144.16 g of a crude product. The crude product was a mixture ofthe target compounds Z-3,7-dimethyl-2,7-octadienyl propionate andE-3,7-dimethyl-2,7-octadienyl propionate at a ratio of 33:67. The crudeproduct was fractionated under vacuum distillation to obtain 58.56 g ofa mixture (87.6 to 95.5% GC, an isomer ratio Z:E of 42:58 to 18:84,yield including initial distillate with low purity: 51%) of the targetcompounds Z-3,7-dimethyl-2,7-octadienyl propionate andE-3,7-dimethyl-2,7-octadienyl propionate.

3,7-Dimethyl-2,7-octadienyl propionate (95.5% GC)

Isomer ratio Z:E=29:71.

Yellowish oil

Boiling point: 81-85° C./399 Pa.

IR (D-ATR): ν=3073, 2971, 2939, 1738, 1650, 1462, 1377, 1180, 1081, 887cm⁻¹.

¹H-NMR (500 MHz, CDCl₃): δ=1.13 (3×0.29H, t, J=7.6 Hz, Z), 1.13(3×0.71H, t, J=7.6 Hz), 1.69 (3H, br. s, Z & E), 1.70 (3H, br. s, Z &E), 1.96-2.03 (4×0.71+2×0.29H, m, Z & E), 2.08 (2×0.29H, br. t, J=7.7Hz, Z), 2.31 (2×0.29H, q, J=7.6 Hz, Z), 2.32 (2×0.71H, q, J=7.6 Hz, E),4.55 (0.29H, br. s, Z), 4.56 (0.29H, br. s, Z), 4.58 (0.71H, br. s, E),4.59 (0.71H, br. s, E), 4.66 (2H, br. s, Z & E), 4.70 (2H, br. s, Z &E), 5.31-5.38 (1H, m, Z & E) ppm.

¹³C-NMR (125 MHz, CDCl₃): δ=9.10 (Z & E), 16.31 (E), 22.32 (Z & E),23.39 (Z), 25.44 (E), 25.97 (Z), 27.57 (Z & E), 31.57 (Z), 37.24 (E),37.40 (Z), 39.01 (E), 60.87 (Z), 61.20 (E), 109.94 (E), 109.98 (Z),118.48 (E), 119.23 (Z), 142.05 (E), 142.61 (Z), 145.47 (Z), 145.62 (E),174.46 (Z), 174.47 (E) ppm.

GC-MS (EI, 70 eV): (Z)-isomer: 29, 41, 57 (base peak), 69, 81, 93, 107,121, 136, 154, 167, 181, 195; (E)-isomer: 29, 41, 57 (base peak), 69,81, 93, 107, 121, 136, 154, 167, 181, 195.

Example 23: Production No. 2 of 3,7-dimethyl-2,7-octadienyl propionate[R³═CH₂CH₃ in General Formula (7)]

Under a nitrogen atmosphere, a mixture of 26.2 g of pyridine and 200 mlof t-butyl methyl ether with 34.1 g of the mixture ofZ-3,7-dimethyl-2,7-octadienol and E-3,7-dimethyl-2,7-octadienol at aratio of 19:81 obtained in Example 21 was stirred on ice, and 25.6 g ofpropionyl chloride was dropwise added thereto at 20° C. or less over 20minutes. The reaction mixture was stirred at room temperature for 2.5hours and then cooled on ice, and a saturated aqueous sodium hydrogencarbonate solution was added thereto. The separated organic phase wassubjected to common work-up of washing, drying and concentration toobtain 43.90 g of a crude product. The crude product was fractionated byvacuum distillation to obtain 31.90 g of a mixture (95.8% GC, a isomerratio Z:E=19:81, yield including initial distillate with low purity:87%) of the target compounds Z-3,7-dimethyl-2,7-octadienyl propionateand E-3,7-dimethyl-2,7-octadienyl propionate. Components of the mixturewere identical with those in Example 22 except for the isomer ratio.

Example 24: Simultaneous Production of a Mixture of7-methyl-3-methylene-7-octenal (2) and 3,7-dimethyl-2,7-octadienal (5)

First, 10.0 g of 7-methyl-3-methylene-7-octenal diethyl acetal (83.6%GC) and 30 g of a mixture of water, acetic acid and formic acid at aweight ratio of 10:5:1 were stirred at 70 to 80° C. for 8 hours. Thereaction mixture was cooled, then diluted with toluene, and washed, andthen the organic phase was separated. The organic phase contained amixture of the target compounds 7-methyl-3-methylene-7-octenal,Z-3,7-dimethyl-2,7-octadienal and E-3,7-dimethyl-2,7-octadienal at a GCarea ratio of 33:26:41. Components of the mixture were the same as thosein Example 8 and Example 15 although the isomer ratio was different. Theorganic phase was not further purified and was subjected to the nextstep.

Example 25: Simultaneous Production of a Mixture of7-methyl-3-methylene-7-octenol (3) and 3,7-dimethyl-2,7-octadienol (6)

Under a nitrogen atmosphere, a mixture of 1.50 g of sodium borohydride,50 ml of a 20% aqueous sodium hydroxide solution and 50 ml of water wasstirred on ice, and a mixture of 50 ml of ethanol with the mixture of7-methyl-3-methylene-7-octenal, Z-3,7-dimethyl-2,7-octadienal andE-3,7-dimethyl-2,7-octadienal at a GC area ratio of 33:26:41 obtained inExample 24 was dropwise added thereto at 15° C. or less over 30 minutes.The reaction mixture was warmed to room temperature and stirred for 16hours, and then the organic phase was separated. The organic phase wassubjected to common work-up of washing, drying and concentration toobtain 5.63 g of a crude product. The crude product was a mixture (71.9%GC, yield: 71%) of the target compounds 7-methyl-3-methylene-7-octenol,Z-3,7-dimethyl-2,7-octadienol and E-3,7-dimethyl-2,7-octadienol at a GCarea ratio of 32:28:41. Components of the mixture were the same as thosein Example 11 and Example 19 although the isomer ratio is different. Thecrude product was not further purified and was subjected to the nextstep.

Example 26: Simultaneous Production of a Mixture of7-methyl-3-methylene-7-octenyl propionate [R³═CH₂CH₃ in General Formula(4)] and 3,7-dimethyl-2,7-octadienyl propionate [R³═CH₂CH₃ in GeneralFormula (7)]

Under a nitrogen atmosphere, a mixture of 20.0 g of pyridine and 20.0 gof tetrahydrofuran with 5.48 g of the mixture (71.9% GC) of7-methyl-3-methylene-7-octenol, Z-3,7-dimethyl-2,7-octadienol andE-3,7-dimethyl-2,7-octadienol at a ratio 32:28:41 obtained in Example 25was stirred on ice, and 4.00 g of propionyl chloride was added thereto.The reaction mixture was stirred on ice for 2 hours and at roomtemperature for 17 hours, and water was added thereto to stop thereaction. Hexane was added thereto, and the separated organic phase wassubjected to common work-up of washing, drying and concentration toobtain 7.15 g of a crude product. The crude product was a mixture of thetarget compounds 7-methyl-3-methylene-7-octenyl propionate,Z-3,7-dimethyl-2,7-octadienyl propionate andE-3,7-dimethyl-2,7-octadienyl propionate at a ratio of 30:27:43. Thecrude product was distilled under reduced pressure to obtain 5.03 g of amixture (89.3% GC, yield including initial distillate having 54.9% GC:89%) of the target compounds 7-methyl-3-methylene-7-octenyl propionate,Z-3,7-dimethyl-2,7-octadienyl propionate andE-3,7-dimethyl-2,7-octadienyl propionate at a ratio of 30:27:44.

Mixture of 7-methyl-3-methylene-7-octenyl propionate,Z-3,7-dimethyl-2,7-octadienyl propionate andE-3,7-dimethyl-2,7-octadienyl propionate at a Ratio of 30:27:44

Boiling point: 75° C./332 Pa.

Components of the mixture were the same as those in Example 12 andExample 22 although the isomer ratio was different.

1. A method for producing 3,7-dimethyl-2,7-octadienal of Formula (5):

the method comprising steps of: hydrolyzing a7-methyl-3-methylene-7-octenal acetal compound of General Formula (1):

wherein R¹ and R², which may be the same or different, are each an alkylgroup having 1 to 6 carbon atoms, or are bonded to each other to form adivalent alkylene group having 2 to 12 carbon atoms, to obtain7-methyl-3-methylene-7-octenal of Formula (2):

and isomerizing the 7-methyl-3-methylene-7-octenal (2) in the presenceof a base to obtain the 3,7-dimethyl-2,7-octadienal (5).
 2. The methodof claim 1 further comprising: a step of coupling a nucleophilic reagentexpressed as a 3-methyl-3-butenyl M of General Formula (8):

wherein M is a cationic moiety, with an acetal compound of GeneralFormula (9):

wherein R¹ and R², which may be the same or different, are each an alkylgroup having 1 to 6 carbon atoms, or are bonded to each other to form adivalent alkylene group having 2 to 12 carbon atoms, and X is a leavinggroup, to obtain the 7-methyl-3-methylene-7-octenal acetal compound ofGeneral Formula (1).
 3. The method of claim 1 further comprising:reducing the 3,7-dimethyl-2,7-octadienal (5) to obtain3,7-dimethyl-2,7-octadienol of Formula (6):

and esterifying the 3,7-dimethyl-2,7-octadienol (6) to obtain the3,7-dimethyl-2,7-octadienyl carboxylate compound of General Formula (7).


4. A method for producing a 3,7-dimethyl-2,7-octadienyl carboxylatecompound of General Formula (7):

wherein R³ is a hydrogen atom or a monovalent hydrocarbon group having 1to 6 carbon atoms, the method comprising steps of: hydrolyzing a7-methyl-3-methylene-7-octenal acetal compound of General Formula (1):

wherein R¹ and R², which may be the same or different, are each an alkylgroup having 1 to 6 carbon atoms, or are bonded to each other to form adivalent alkylene group having 2 to 12 carbon atoms, to obtain7-methyl-3-methylene-7-octenal of Formula (2):

and isomerizing the 7-methyl-3-methylene-7-octenal (2) in the presenceof a base to obtain 3,7-dimethyl-2,7-octadienal of Formula (5):

reducing the 3,7-dimethyl-2,7-octadienal (5) to obtain3,7-dimethyl-2,7-octadienol of Formula (6):

and esterifying the 3,7-dimethyl-2,7-octadienol (6) to obtain the3,7-dimethyl-2,7-octadienyl carboxylate compound (7).
 5. A7-methyl-3-methylene-7-octenal acetal compound of General Formula (1):

wherein R¹ and R², which may be the same or different, are each an alkylgroup having 1 to 6 carbon atoms, or are bonded to each other to form adivalent alkylene group having 2 to 12 carbon atoms.